Abstract
Selective vagal nerve stimulation (sVNS) has been demonstrated to lower blood pressure (BP) in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs) are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight), the animals’ mean arterial blood pressures (MAPs) decreased significantly, while the heart rates (HRs) were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.
Highlights
ObjectivesIn the context of the above-mentioned observation that Converting enzyme inhibitors (CEIs) medications possibly influence the baroreflex, the aim of the present study was to elucidate whether intravenously administered enalapril interferes with antihypertensive selective vagal nerve stimulation (sVNS) in a male Wistar rat model
Arterial hypertension is a common disease that affects millions of patients
In our effort to develop a neuromodulation treatment of therapy-refractory arterial hypertension, we recently proposed a technique of selective vagal nerve stimulation with a multichannel cuff electrode (MCE) that activates the baroreflex in rats [2]
Summary
In the context of the above-mentioned observation that CEI medications possibly influence the baroreflex, the aim of the present study was to elucidate whether intravenously administered enalapril interferes with antihypertensive sVNS in a male Wistar rat model
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